Abstract B034: A scoping review of carcinogenic potential in prostate cancer from 40+ years of functional vitamin D and K deficiency
Authors: Tim R.D. Oliver, Belinda Nedjai
Journal: Cancer Research (2023)

Abstract Introduction: Carcinogenesis is a form of accelerated genetic “Darwinian” evolution. Many cells start genetic change. Tobacco tar, an example of extensively researched carcinogen, demonstrates that it takes chronic exposure over 40+ years, accumulating mutations before death with multiple genetic events. Terminal acceleration often includes loss of major histocompatibility (MHC) antigens. Other co-carcinogens, genetic inheritance and chronic inflammation accelerates this process. Experiments, showing that malignant change induced in vitro is much faster than in vivo, suggest that other factors impact on the pace of malignant evolution. Two such factors (DNA repair and immune surveillance) are the best established. As considerable research is targeting DNA repair gene damage, this abstract focuses on latent immunity (less dependent on MHC system than T cell immunity) and its under-performance in carcinogenesis due to Vitamin D and K deficiency. Literature Review terms: Vitamin D(VD), Vitamin K(VK), Cancer, Carcinogenesis, Latent Immunity. Results: Three pieces of evidence that functional long-term VD and VK deficiency could have oncogenic potential were identified. The first was discovery that patients with chronic inflammation had hypermethylation of the VD receptor resulting in failure of the liver to convert stored VD into its active forms. Cancer patients with higher extent of methylation of VD receptor had worse clinical outcomes. Such deficiency is associated with reduced innate immunity due to macrophage dysfunction and this deficiency could increase microbiome dysbiosis. This suggestion is supported by studies linking PCa with 40+ years of persistent infection with the sun-sensitive microaerophilic bacterium Cutibacterium acnes and VD deficiency is linked with increased cancer but limited benefits in VD trials. The second observation is the demonstration that VK2 (Menaquinone) not VK1 (Phylloquinone) deficiency increased risk of PCa. These authors also showed that undercarboxylated osteocalcin, a biomarker of VK2 deficiency, was also linked with risk of PCa. The third observation was evidence from in-vitro breast cancer cell-line studies that Calcitriol plus K2 was synergistic in cytotoxicity assays. Measuring these effects, through the study of the biological age using methylation-based measures PhenoAge and GrimAge because of their relationship between biological aging and cancer, could be useful to monitor in future trials. Conclusions: Combined VD and VK studies have been found safe and beneficial in bone health. This limited review justifies further exploration of this combination in cancer patients. Using serial epigenetic clock scores is justified, given that these clocks are known to improve from diet and exercise interventions. Functional deficiency of VD and VK could be acting as co-carcinogens through enhanced inflammatory process, a precursor in many cancers including those without known carcinogen involvement such as PCa and also involved in accelerating tumour growth after primary treatment. Citation Format: Tim R.D. Oliver, Belinda Nedjai. A scoping review of carcinogenic potential in prostate cancer from 40+ years of functional vitamin D and K deficiency [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B034.